1. Field of the Invention
This invention relates to (i) novel 2-amino-4H-3,1-benzoxazin-4-ones and the pharmaceutically acceptable, non-toxic esters and salts thereof; (ii) the use of these compounds as enzyme inhibitors in animals; (iii) pharmaceutical compositions comprising a compound of this invention and at least one pharmaceutical excipient; and (iv) processes for preparing the compounds of this invention.
2. Related Art
The compounds of this invention are 2-amino-substituted derivatives of 4H-3,1-benzoxazinones having the following structure: ##STR2## 2-Amino-4H-3,1-benzoxazin-4-one, and the corresponding compounds in which both hydrogen atoms of the 2-amino group have been replaced by a substituent such as alkyl, have been described previously; see, for example, Monatsch, 95 (3) 950-960 and U.S. Pat. No. 3,450,700 assigned to The Upjohn Company. 2-Amino-4H-3,1-benzoxazin-4-ones in which only one hydrogen atom of the 2-amino group has been replaced with a phenyl substitutuent are described by Sheehan et al., J. Org. Chem. 29, 3599-3601, 1964 and Herlinger, Angew. Chem. 76, 437, 1964. Corresponding compounds in which the 2-amino substituent is a mono- or di-methyl substituted morpholinyl group are disclosed in W. German Patent No. 29-14-915 to BASF. None of these compounds are reported to have activity as physiological enzyme inhibitors.
A few 4H-3,1-benzoxazin-4-ones are known to possess enzyme-inhibitory activity. Teshima et al. have disclosed various 2-alkyl-4H-3,1-benzoxazin-4-ones reported to be active as enzyme inhibitors (J. Biol. Chem, 257, 5085-5091, 1982), and 4H-3,1-benzoxazin-2,4-dione has been disclosed as having some enzyme inhibitory activity (Moorman, A. R., and Abeles, R. H. J. Amer. Chem. Soc. 104, 6785-6786, 1982).